The field of this invention is drug delivery, particularly localized drug delivery.
One of the most complex and difficult problems that has plagued the medical profession and pharmaceutical industry for decades is the problem of achieving a therapeutic concentration of a drug locally at a target site within the body without producing unwanted systemic side effects. Parenteral or oral therapy of substances directed at treating disease in a particular internal organ or at a particular internal site must often be given in amounts dependent upon achieving critical systemic blood levels that can produce devastating side effects at other areas in the body. In yet other embodiments, the pharmacological agent being delivered may be expensive, making systemic administration costly. As such, systemic routes of administration are not always desirable or acceptable.
A number of protocols and delivery vehicles have been developed for use in local or regional administration of an active agent, where the agent is administered in such a way that it is confined to a particular area or location of the body, e.g. at or proximal to the target tissue. Such protocols include those in which the agent is delivered to the patient in a vehicle that acts as a depot for the agent, where a variety of synthetic and natural polymeric compositions have been used as depots in the local administration of active agents.
While a number of different protocols and vehicles have been developed for use in the local delivery of active agents, there continues to be a need for the development of new protocols of local agent delivery. Of particular interest would be the development of local delivery protocol which could provide for local delivery of an active agent into an interstitial space of a patient, preferably using a catheter based delivery system.
U.S. Patents of interest include: U.S. Pat. Nos. 4,459,977; 4,689,041; 4,934,996; 5,011,468; 5,533,957; 5,597,377; 5,824,071; 5,885,238; 5,913,842 and 5,922,687. Also of interest are: Mann et al., Proc. Nat""l Acad. Sci. USA (May 1999) 96:6411-6; von der Leyen et al., Hum. Gene Ther. (September 1999) 10:2355-64; Baumbach et al., Catheter Cardiovasc. Interv. (May 1999) 47:102-106.
Methods are provided for locally administering an agent to a host. Specifically, the subject methods provide for the local administration of an agent to an interstitial space of a host. In the subject methods, an agent is retroinfused into a vessel of a host, typically a vein, under conditions sufficient for the agent to enter an interstitial space of the host proximal to the vessel location into which the agent is retroinfused. In practicing the subject methods, the agent is administered to the host in combination with the production of vascular stress at the site of administration, where the vascular tissue stress is sufficient to provide for transport of the agent from the vascular site of deposition into the target interstitial space. In a preferred embodiment, the agent is retroinfused at a pressure sufficient to provide for mechanical stress on the vessel proximal to the target interstitial space. Also provided are kits for use in practicing the subject methods. The subject invention finds use in the local administration of a variety of different agents for treatment of a variety of different disease or other conditions.